Roche is developing mericitabine (R7128), an investigational nucleoside inhibitor of NS5B HCV polymerase with antiviral activity against HCV genotypes 1-6.
Feb 14 2013
Roche Polymerase Nuc Mericitabine, study results reported from JUMP-C
Download the PDF here or view full text at NATAP.
In conclusion, when administered for 24 weeks at a dosage of 1,000 mg twice daily as part of a response-guided combination with peginterferon alfa-2a/ribavirin, mericitabine produced higher SVR rates than a standard 48-week course of peginterferon alfa-2a/ribavirin and was extremely well tolerated, without any documented antiviral resistance.
Despite these results, recent favorable results achieved with all-oral direct-acting antiviral combination regimens suggest that future development scenarios for mericitabine will need to include combinations with other direct-acting antiviral agents.
The high barrier to resistance, and the good tolerability and safety profile, make mericitabine potentially useful in combination with other direct-acting antivirals that have a lower barrier to resistance and may be more potent.
Ongoing studies will provide data on the efficacy and safety of mericitabine in various interferon-free combinations with protease inhibitors and non-nucleoside polymerase inhibitors, and in a quadruple combination regimen with a protease
inhibitor and peginterferon/ribavirin in the most difficult-to-treat populations...continued @ NATAP.
HIV and Hepatitis - HCV Polymerase Inhibitor Mericitabine Boosts Interferon/Ribavirin Cure Rate
Healio - Mericitabine improved outcomes from peginterferon/ribavirin therapy for chronic HCV
New therapeutic strategies in HCV: polymerase inhibitors
INTERFERON-FREE TREATMENT WITH A COMBINATION OF MERICITABINE AND
DANOPREVIR/R WITH OR WITHOUT RIBAVIRIN IN TREATMENT-NAIVE HCV GENOTYPE
The hepatitis C treatment landscape is rapidly evolving. The recent regulatory approval of first-generation protease inhibitors has resulted in a new standard of care for genotype 1 patients, consisting of peginterferon alfa/ribavirin (RBV) in combination with telaprevir or boceprevir, with sustained virological response (SVR) rates of 68-75% achievable in treatment-naive patients.[1-3] · However, safety and tolerability remain suboptimal. The benefits of adding one direct-acting antiviral agent (DAA) to peginterferon alfa/RBV remain limited due to the underlying safety and tolerability issues associated with interferon-based treatment. · An all-oral, interferon-free DAA combination treatment would fill an unmet medical need and potentially further change the treatment paradigm. · Two DAAs currently in phase II clinical development are mericitabine (MCB) and danoprevir (DNV; RG7227). · MCB is a selective and non-cytotoxic hepatitis C virus (HCV) polymerase inhibitor which is active against all HCV genotypes and has a high barrier to resistance.[5-7] · DNV is a potent, macrocyclic, HCV protease inhibitor that has equipotent activity against HCV genotypes 1, 4 and 6 in vitro.[8,9] · The phase I INFORM-1 study demonstrated that treatment with a combination of these two DAAs for 13 days resulted in significant reductions in HCV RNA in both treatment-naive and prior null responders and was well tolerated. · Co-administration of ritonavir with lower doses of DNV has since been shown to decrease the overall exposure of DNV while maintaining potent antiviral activity. · The phase IIb INFORM-SVR study is investigating the safety and efficacy of response-guided treatment with MCB in combination with ritonavir-boosted DNV (DNVr) with and without RBV for 12 or 24 weeks in treatment-naive patients with genotype (G) 1 chronic HCV infection. · Here, results from a 12-week post-treatment interim analysis of the INFORM-SVR study are presented.
SVR24 AMONG G1/4 TREATMENT-NAIVE PATIENTS RECEIVING MERICITABINE IN COMBINATION WITH PEG-IFNα-2A/RBV: FINAL ANALYSIS FROM THE JUMP-C STUDY
In treatment-naive genotype 1 or 4 patients, a response-guided regimen that included 24 weeks of therapy with the combination of mericitabine plus peginterferon alfa-2a (40KD)/ribavirin produced SVR24 rates that were 20%
higher than those achieved with placebo plus peginterferon alfa-2a (40KD)/ribavirin (56.8% vs. 36.5%, respectively).
The mericitabine-based combination regimen produced consistently higher SVR rates in patients with and without cirrhosis and in patients with CC and non-CC IL28B genotypes.
· Although the numbers of patients were small, logistic regression analysis showed no obvious difference in rates of SVR24
between HCV genotype 1a vs. 1b patients.
· Combination therapy with mericitabine was safe, well tolerated and demonstrated a high barrier to resistance.
· The unique combination of potent antiviral activity, a high barrier to resistance, excellent safety profile and low potential for pharmacokinetic drug-drug interactions make mericitabine an attractive potential component of antiviral regimens for chronic hepatitis C..........continued @ NATAP
April 24 2012
Winners, Losers From EASL Hep C Data Dump
A Roche study combining the nucleoside polymerase inhibitor mericitabine, a protease inhibitor danoprevir and ribavirin proved to be relatively unsuccessful, with a cure rate of 41% overall (71% in genotype 1b patients and
just 26% in the harder-to-treat genotype 1a patients.)..................
Product Description- R-7128(RG 7128; Mericitabine; PSI 6130 diisobutyrate) is
RNA-directed RNA polymerase (NS5B) inhibitor treatment of hepatitis C virus